Potent neutralization by monoclonal human IgM against SARS‐CoV‐2 is impaired by class switch
Ilaria Callegari, Mika Schneider, Giuliano Berloffa, Tobias Mühlethaler, Sebastian Holdermann, Edoardo Galli, Tim Roloff, R. Boss, Laura Infanti, Nina Khanna, Adrian Egli, Andreas Buser, Gert Zimmer, Tobias Derfuß, Nicholas Sanderson
Abstract
To investigate the class-dependent properties of anti-viral IgM antibodies, we use membrane antigen capture activated cell sorting to isolate spike-protein-specific B cells from donors recently infected with SARS-CoV-2, allowing production of recombinant antibodies. We isolate 20, spike-protein-specific antibodies of classes IgM, IgG, and IgA, none of which shows any antigen-independent binding to human cells. Two antibodies of class IgM mediate virus neutralization at picomolar concentrations, but this potency is lost following artificial switch to IgG. Although, as expected, the IgG versions of the antibodies appear to have lower avidity than their IgM parents, this is not sufficient to explain the loss of potency.